New Pathophysiological Pathways Involved in Iron Metabolism Disorder in Heart Failure (IRON-PATH II)

New Pathophysiological Pathways Involved in Iron Metabolism Disorder in Heart Failure: The IRON-PATH II Investigator Initiated Study

The aim of our study is to understand the biological pathways involved in the occurrence of IDy in patients with HF since ID is very common and supposes a negative impact in terms of clinical outcomes in these patients. In this context, a deeper understanding of the mechanisms involved in the development of ID in these patients and the impact on the altered biological pathways after iron replenishment will pave the way for an improvement and simplification of the preventive strategies in patients with HF.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Iron Carboxymaltose

Detailed Description

The IRON-PATH II Project is a pre-clinical and clinical study designed as a multicenter, prospective, observational (non-interventional), investigator initiated study. The total number of patients to be recruited will be 210 (80 patients without ID and 130 patients with ID). Patients will be recruited during 12 months in 7 centers across Spain and Portugal and followed for a fixed period of 12 months. The primary objective of the clinical study is to define pathways associated with systemic and tissue ID in HF patients compared with non-ID HF patients and explore the change in the patterns of pathway activation/suppression after irons status normalization in ID patients with intravenous iron treatment using an integrative omics and systems biology approach including whole-genome analysis of gene expression (transcriptome), protein synthesis (proteomics) and metabolic characterization (metabolomics) from blood samples. Key secondary objectives will include changes in patient-reported outcomes (PROMs) such as QoL, patient-reported experience measures (PREMs), the occurrence of events, among others between those with and without ID. The aims of the pre-clinical study is to confirm previous findings of the IRONPATH I study and to explore in vitro interventions in cardiac cells models with iron deficiency.

• Study Type: Observational
• Enrollment (Anticipated): 210

Contacts and Locations

• Study Contact: Name: Josep Comín Colet, MD, PhD; Phone Number: +34 932607078; Email: jcomin@bellvitgehospital.cat
• Study Contact Backup: Name: Maria del Mar Ras Jimenez, MD; Phone Number: +34 932607078; Email: mras@bellvitgehospital.cat

Study Locations

• Spain
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • Hospital Universitari de Bellvtige
      • Contact: Josep R Comin, MD, PhD; Phone Number: 2274 +34-933-35-70-11; Email: jcomin@bellvitgehospital.cat
      • Contact: Maria del Mar Ras Jimenez, MD; Phone Number: 2274 +34-933-35-70-11; Email: mras@bellvitgehospital.cat
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • University Hospital Bellvitge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study cohort will be a multicenter, observational, prospective, cross-sectional and longitudinal nested case-control sample of 210 patients with (130 cases) and without (80 controls) ID according to the FAIR-HF (27) (serum ferritin <100 mg/L or transferrin saturation [%TSAT]<20% if ferritin is between 100-300mg/L), recruited for the specific purpose of the IRON-PATH II study.

Description

Inclusion Criteria:

• Age ≥ 18 years old.
• HF diagnosis according to European Society of Cardiology
• LVEF≤50% (systolic HF).
• Patients receiving oral standard medication for chronic HF.
• Iron status evaluated in the last 3 months.
• Written informed consent.

Exclusion Criteria:

• Age<18 years old.
• Intravenous or oral iron administration or under treatment with ESA (erythropoiesis-stimulating agents) in the previous 3 months.
• Planned cardiac resynchronization therapy (CRT), revascularization and other major interventions including heart transplant or left ventricular assist device (LVAD) implantation in the next 3 months in patients with ID.
• Planned uptitration of guideline-mandatory HF-modifying drugs in the next 3 months (except iron repletion) in patients with ID.
• Moderate or severe anaemia (Hb<11 g/dL).
• The patient is unable or unwilling to give the informed consent to participate.
• Unstable patients with signs of fluid overload or low cardiac output at the moment of enrollment.
• Life expectancy less than 1 year (excluding HF).
• The patient is considered not to be an adequate candidate for this study according to the decision of the local investigator.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with iron deficiency	Drug: Iron Carboxymaltose; Iron supplementation when is needed according to usual care
Patients without iron deficiency

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To define pathways associated with iron deficiency (ID) in heart failure (HF) patients compared with non-ID HF patients	Using an integrative omics and systems biology approach including whole-genome analysis of gene expression (transcriptome), protein synthesis (proteomics) and metabolic characterization (metabolomics) from blood samples.	Twelve months after inclusion the patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Biomarkers (New York Heart Association [NYHA)	Comparison between ID and non ID patients	Twelve months after inclusion the patient
Improvement of self-care using a validated scale (European Heart Failure Self-Care Behavior Scale).	Comparison between ID and non ID patients	Twelve months after inclusion the patient
Patient-reported experience measures (PREMs) (IEXPAC)	Comparison between ID and non ID patients	Twelve months after inclusion the patient
Prognostic biomarkers (NT-proBNP)	Comparison between ID and non ID patients	Twelve months after inclusion the patient
Occurrence of events (all-cause death, HF-clinically related admissions, CV admissions)	Comparison between ID and non ID patients	Twelve months after inclusion the patient
Functional Biomarkers (6-minutes walking test [6MWT] distance)	Comparison between ID and non ID patients	Twelve months after inclusion the patient
Improvement of quality of life using a validated questionnaire (EUROQOL - 5D)	Comparison between ID and non ID patients	Twelve months after inclusion the patient

Collaborators and Investigators

• Sponsor: Hospital Universitari de Bellvitge
• Investigators: Principal Investigator: Josep Comin Colet, MD, PhD, Bellvitge Biomedical Research Institute (IDIBELL) - Hospital Universitari de Bellvitge

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: July 15, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 11, 2021

Study Record Updates

• Last Update Posted (Estimate): December 13, 2022
• Last Update Submitted That Met QC Criteria: December 12, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Iron Deficiency; Machine Learning; Outcomes Research; Multi-Omics Approaches
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Metabolic Diseases; Iron Metabolism Disorders
• Other Study ID Numbers: IDIBELL - EOM019/21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No